The contract is to evaluate two selective CCR2R antagonists, (YF476 and JNJ-26070109) for pancreatic cancer prevention in preclinical models. Specifically, the Contractor shall establish the optimal dose and maximal tolerated dose (MTD) of these two antagonists in mice and then assess the pancreatic cancer prevention efficacy in p48Cre/+-LSL-KrasG12D/+ transgenic mouse model of pancreatic cancer. In addition, the Contractor shall explore critical biomarkers of pharmacodynamic efficacy, which will be applicable to early-phase clinical studies.